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AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic

The cell surface proteome controls numerous cellular functions including cell migration and adhesion, intercellular communication and nutrient uptake. Cell surface proteins are controlled by acute changes in protein abundance at the plasma membrane through regulation of endocytosis and recycling (en...

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Autores principales: Ross, Eden, Ata, Rehman, Thavarajah, Thanusi, Medvedev, Sergei, Bowden, Peter, Marshall, John G., Antonescu, Costin N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444004/
https://www.ncbi.nlm.nih.gov/pubmed/26010094
http://dx.doi.org/10.1371/journal.pone.0128013
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author Ross, Eden
Ata, Rehman
Thavarajah, Thanusi
Medvedev, Sergei
Bowden, Peter
Marshall, John G.
Antonescu, Costin N.
author_facet Ross, Eden
Ata, Rehman
Thavarajah, Thanusi
Medvedev, Sergei
Bowden, Peter
Marshall, John G.
Antonescu, Costin N.
author_sort Ross, Eden
collection PubMed
description The cell surface proteome controls numerous cellular functions including cell migration and adhesion, intercellular communication and nutrient uptake. Cell surface proteins are controlled by acute changes in protein abundance at the plasma membrane through regulation of endocytosis and recycling (endomembrane traffic). Many cellular signals regulate endomembrane traffic, including metabolic signaling; however, the extent to which the cell surface proteome is controlled by acute regulation of endomembrane traffic under various conditions remains incompletely understood. AMP-activated protein kinase (AMPK) is a key metabolic sensor that is activated upon reduced cellular energy availability. AMPK activation alters the endomembrane traffic of a few specific proteins, as part of an adaptive response to increase energy intake and reduce energy expenditure. How increased AMPK activity during energy stress may globally regulate the cell surface proteome is not well understood. To study how AMPK may regulate the cell surface proteome, we used cell-impermeable biotinylation to selectively purify cell surface proteins under various conditions. Using ESI-MS/MS, we found that acute (90 min) treatment with the AMPK activator A-769662 elicits broad control of the cell surface abundance of diverse proteins. In particular, A-769662 treatment depleted from the cell surface proteins with functions in cell migration and adhesion. To complement our mass spectrometry results, we used other methods to show that A-769662 treatment results in impaired cell migration. Further, A-769662 treatment reduced the cell surface abundance of β1-integrin, a key cell migration protein, and AMPK gene silencing prevented this effect. While the control of the cell surface abundance of various proteins by A-769662 treatment was broad, it was also selective, as this treatment did not change the cell surface abundance of the transferrin receptor. Hence, the cell surface proteome is subject to acute regulation by treatment with A-769662, at least some of which is mediated by the metabolic sensor AMPK.
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spelling pubmed-44440042015-06-16 AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic Ross, Eden Ata, Rehman Thavarajah, Thanusi Medvedev, Sergei Bowden, Peter Marshall, John G. Antonescu, Costin N. PLoS One Research Article The cell surface proteome controls numerous cellular functions including cell migration and adhesion, intercellular communication and nutrient uptake. Cell surface proteins are controlled by acute changes in protein abundance at the plasma membrane through regulation of endocytosis and recycling (endomembrane traffic). Many cellular signals regulate endomembrane traffic, including metabolic signaling; however, the extent to which the cell surface proteome is controlled by acute regulation of endomembrane traffic under various conditions remains incompletely understood. AMP-activated protein kinase (AMPK) is a key metabolic sensor that is activated upon reduced cellular energy availability. AMPK activation alters the endomembrane traffic of a few specific proteins, as part of an adaptive response to increase energy intake and reduce energy expenditure. How increased AMPK activity during energy stress may globally regulate the cell surface proteome is not well understood. To study how AMPK may regulate the cell surface proteome, we used cell-impermeable biotinylation to selectively purify cell surface proteins under various conditions. Using ESI-MS/MS, we found that acute (90 min) treatment with the AMPK activator A-769662 elicits broad control of the cell surface abundance of diverse proteins. In particular, A-769662 treatment depleted from the cell surface proteins with functions in cell migration and adhesion. To complement our mass spectrometry results, we used other methods to show that A-769662 treatment results in impaired cell migration. Further, A-769662 treatment reduced the cell surface abundance of β1-integrin, a key cell migration protein, and AMPK gene silencing prevented this effect. While the control of the cell surface abundance of various proteins by A-769662 treatment was broad, it was also selective, as this treatment did not change the cell surface abundance of the transferrin receptor. Hence, the cell surface proteome is subject to acute regulation by treatment with A-769662, at least some of which is mediated by the metabolic sensor AMPK. Public Library of Science 2015-05-26 /pmc/articles/PMC4444004/ /pubmed/26010094 http://dx.doi.org/10.1371/journal.pone.0128013 Text en © 2015 Ross et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ross, Eden
Ata, Rehman
Thavarajah, Thanusi
Medvedev, Sergei
Bowden, Peter
Marshall, John G.
Antonescu, Costin N.
AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic
title AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic
title_full AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic
title_fullStr AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic
title_full_unstemmed AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic
title_short AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic
title_sort amp-activated protein kinase regulates the cell surface proteome and integrin membrane traffic
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444004/
https://www.ncbi.nlm.nih.gov/pubmed/26010094
http://dx.doi.org/10.1371/journal.pone.0128013
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